The ultimate objective of this project is, first, to develop quantitatively the fundamental facts and laws concerning the quantal nature of hippocampal neurons. Second, this background information will then be used as part of an effort to determine the mechanisms responsible for the well-known phenomenon of long-term synaptic potentiation (LTP) in this system. The particular synapse selected for study is the granule cell mossy fibre to CA3 pyramidal cell synapse. The following specific aims will be pursued in the order listed using current- and voltage-clamp techniques, the results of which will be interpreted with the aid of computer simulations. (1) Several methods will be used to evaluate the approximate electrotonic structure of the postsynaptic cell for the purpose of understanding the effect of the passive cable properties on synaptic events recorded in the soma. (2) The statistical features of spontaneous and evoked quantal release will be analyzed to determine whether the classical laws of quantal release apply to these synapses. (3) The kinetics of LTP will be examined under various ionic and stimulation conditions to compare the results obtained using the traditional extracellular recording methods with those obtained intracellularly under current- and voltage-clamp. (4) Five hypotheses for LTP will be tested.